LATEST TECHNOLOGY IN Safe handling & Recovery OF Solvents in Pharma Industry TYPICAL SOLVENT USE IN Pharma Industry Usage of solvents in an API process development is for: Diluent to carry out reaction To produce high purity product Consistent quality of the product Higher yields Volume efficiency Operability Solvent are used about 80 to 90% of mass Solvents are dominant in determining the toxicity of the process RISK FACTORS Safety Environmental Impact 1
Solvent use DEVELOPMENT STAGE Scientist have to consider Solubility selection basis. Polarity refers to s separation of electric charge. Volatility tendency to vaporize at different temperatures. Cost and easy availability. Melting/Boiling points. Viscosity- resistance of a fluid. Flash Point Corrosiveness. Reactivity. Environmental health and safety SAFETY 2
Green chemistry solvent guide Preferred Water Acetone Ethanol 2-Propanol 1-Propanol Ethyl acetate Isopropyl acetate Methanol MEA 1-Butanol t-butanol Usable Cyclohexane Heptanes Toluene t-butyl Methyl ether Isooctane Acetonitrile 2-MeTHF Xylenes DMSO Acetic acid Ethylene Glycol Undesirable Pentane Hexane's Di-Isopropyl ether Di-ethyl ether Dichloromethane Chloroform Dichloroethane DMF N-Methyl pyrolidine Pyridine Di methyl acetamide Dioxane Di methoxy ethane Benzene Carbon Tetra chloride. SOLVENT IMPACT Solvent forms a major role in API Cost Safety & Hazard Handling & storage Utility consumption Environmental Impact 3
ECONOMY Consumption of 2000 Lts per batch for 10 batch a month Reduction by 5% Recovery improvement by 10% Will save Rs 3.0 Lakhs per month for a 10 batch/month operation directly (reduction, steam cost & recovery improvement) The saving in manpower, storage, handling and environment is bonus. Solvent reduction methods Choosing right solvent- reduce multiple solvent handling. Combine steps of reaction to reduce solvent use - Telescoping. Process loss by better handling Wash and reuse where ever possible Recover and recycle where ever possible. 4
Optimization of Solvent Use Greener solvent selection & substitution Reduce solvents carbon footprint Elimination of highly hazardous solvents Solvent reduction Recovery techniques Novel approaches to separations Novel reaction media (ionic liquids) Solid-state chemistry Bio catalytic routes Solvent recovery methods Wash and reuse. Simple boil over and reuse. Distill and purify binary/ azeotropic /fractional (atmospheric/pressure or vacuum) Per vaporation techniques 5
SAFE HANDLING Close loop hamdling and avoid mannual and drum handling. Proper earthing while handling Avoid flexible piping and use hard pipes. Do not charge solvent into hot reactors/systems. Keep the condenser temperatures within control and monitor them periodically. Store solvent in cool and dry place. Solvent Recovery Improvements Better utility and design of the distillation system. High vacuum distillation better recovery, yield and purity of the product key factors- Joints, vacuum system. Use of vent condenser in Reactors. De scaling frequently of the heat exchangers and reactor jackets. Use of molecular sieve for removal of moisture. 6
Per vaporation methods Is only membrane process where phase transition occurs. The heat of vaporization has to be supplied. The mass transport is achieved lowering the activity of the permeating component on the permeate side by: gas carrier, vacuum or temperature difference. The driving force is the partial pressure difference of the permeate between the feed and permeate streams. The permeate pressure has to be lower than the saturation pressure of the permeant to achieve the separation. Gas carrier Pervaporation Vacuum Pervaporation Temperature difference Pervaporation Figure 2. Schematic draws of pervaporation processes. Per vaporation Applications Usually used for the chemical process industry, but there are other areas of application Food. Farmaceutical industries Enviromental problem Analytical application Since there are many applications a classification that can be useful is given below: Polar/Non polar Volatile organic Dehydration compounds from water Non-aqueous mixtures Aqueous mixtures Alcohols/aromatics (methanol/toluene) } Removal of water from organic solvents. Alcohols/aliphatics (ethanol/hexane) Alcohols from fermentation broths (ethanol, butanol, etc..) Alcohols/ethers (Methanol/MTBE) { Volatile organic contaminants from waste Cyclohexane/benzene } Aromatics/Aliphatic water (aromatics, chlorinated hydrocarbons) Hexane/toluene. Removal of flavor and aroma compounds. Saturated/Unsaturated Butane/butene. Removal of phenolic compounds. C-8 isomers (o-xylene, m-xylene, p-xylene, styrene). Isomers 7
Mechanism of Transport Pervaporation involve a sequence of three steps: Selective sorption Selective diffusion through the membrane. Desorption into a vapor phase on the permeate side. Because of its characteristics, pervaporation is often mistakenly considered as a kind of extractive distillation but VLE Solution- Diffution mechanism. Figure 3. Comparison between VLE and pervaporation Summary Per vaporation Advantages Drawback Low energy consumption. Low investment cost. Better selectivity without thermodynamic limitations. Clean and close operation. No process wastes. Compact and scalable units. Scarce membrane market. Lack of information. Low permeate flows. Better selectivity without thermodynamic limitations. Limited applications: Organic substances dehydration. Recovery of volatile compounds at low concentrations. Separation of azeo tropic mixtures. 8
Summary Per vaporation Membranes: Composite membranes with an elastomeric or glassy polymeric top layer. Thickness: 0.1 to few µm (for top layer) Pore size: Non-porous Driven force: Partial vapor pressure or activity difference. Separation principle: Solution/Diffusion Membrane material: Elastomeric and glassy. Applications: Dehydration of organic solvents. Removal of organic compounds from water. Polar/non-polar. Saturated/unsaturated. Separation of isomers. 9